Goedhart Tine M H J, Bukkems Laura H, Coppens Michiel, Fijnvandraat Karin J, Schols Saskia E M, Schutgens Roger E G, Eikenboom Jeroen, Heubel-Moenen Floor C J I, Ypma Paula F, Nieuwenhuizen L, Meijer K, Leebeek Frank W G, Mathôt Ron A A, Cnossen Marjon H
Department of Pediatric Hematology and Oncology, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Department of Clinical Pharmacology - Hospital Pharmacy, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
TH Open. 2022 Feb 3;6(1):e60-e69. doi: 10.1055/a-1760-0105. eCollection 2022 Jan.
In resource-rich countries, almost all severe hemophilia patients receive prophylactic replacement therapy with factor concentrates to prevent spontaneous bleeding in joints and muscles to decrease the development of arthropathy and risk of long-term disability. Pharmacokinetic (PK)-guided dosing can be applied to individualize factor replacement therapy, as interindividual differences in PK parameters influence factor VIII (FVIII) and FIX activity levels. PK-guided dosing may therefore lead to more optimal safeguarding of FVIII/FIX levels during prophylaxis and on demand treatment. The OPTI-CLOT TARGET study is a multicenter, nonrandomized, prospective cohort study that aims to investigate the reliability and feasibility of PK-guided prophylactic dosing of factor concentrates in hemophilia-A and -B patients in daily clinical practice. At least 50 patients of all ages on prophylactic treatment using standard half-life (SHL) and extended half-life (EHL) factor concentrates will be included during 9 months and will receive PK-guided treatment. As primary endpoint, a minimum of four FVIII/FIX levels will be compared with FVIII/FIX levels as predicted by Bayesian forecasting. Secondary endpoints are the association of FVIII and FIX levels with bleeding episodes and physical activity, expectations and experiences, economic analyses, and optimization of population PK models. This study will lead to more insight in the reliability and feasibility of PK-guided dosing in hemophilia patients. Moreover, it will contribute to personalization of treatment by greater knowledge of dosing regimens needed to prevent and treat bleeding in the individual patient and provide evidence to more clearly associate factor activity levels with bleeding risk.
在资源丰富的国家，几乎所有重型血友病患者都接受凝血因子浓缩物预防性替代治疗，以预防关节和肌肉的自发性出血，减少关节病的发生和长期残疾风险。药代动力学（PK）指导的给药可用于个体化凝血因子替代治疗，因为PK参数的个体差异会影响凝血因子VIII（FVIII）和FIX活性水平。因此，PK指导的给药可能会在预防和按需治疗期间更优化地维持FVIII/FIX水平。OPTI-CLOT TARGET研究是一项多中心、非随机、前瞻性队列研究，旨在调查在日常临床实践中，PK指导的凝血因子浓缩物预防性给药在血友病A和B患者中的可靠性和可行性。在9个月内，将纳入至少50名使用标准半衰期（SHL）和延长半衰期（EHL）凝血因子浓缩物进行预防性治疗的各年龄段患者，并接受PK指导的治疗。作为主要终点，将至少四个FVIII/FIX水平与贝叶斯预测所预测的FVIII/FIX水平进行比较。次要终点包括FVIII和FIX水平与出血事件、身体活动、期望和体验的关联、经济分析以及群体PK模型的优化。这项研究将使人们对PK指导给药在血友病患者中的可靠性和可行性有更多了解。此外，它将有助于实现治疗个体化，因为对预防和治疗个体患者出血所需的给药方案有了更多了解，并为更明确地将凝血因子活性水平与出血风险联系起来提供证据。
